The effect of interleukin-4 and amphiregulin on the proliferation of human airway smooth muscle cells and cytokine release.
Airway smooth muscle (ASM) hyperplasia and angiogenesis are important features associated with airway remodeling. We investigated the effect of IL-4 and amphiregulin, an epidermal growth factor family member, on the proliferation of human ASM cells and on the release of vascular endothelial growth factor (VEGF) and monocyte chemotactic protein (MCP)-1 from human ASM cells. Human ASM cells were growth-arrested for 48 hr and incubated with platelet-derived growth factor (PDGF)- BB, interleukin (IL)-4, amphiregulin, and VEGF to evaluate cell proliferation. The cells were treated with PDGF, IL-4 and amphiregulin to evaluate the release of VEGF, MCP-1. IL-4 suppressed unstimulated and PDGF-stimulated ASM cell proliferation. Amphiregulin stimulated ASM cell proliferation in a dose-dependent manner. VEGF did not have any influence on ASM cell proliferation. IL-4 stimulated VEGF secretion by the ASM cells in a dose-dependent manner and showed added stimulatory effects when co-incubated with PDGF. Amphiregulin did not promote VEGF secretion. IL-4 and amphiregulin showed no stimulatory effects on MCP-1 secretion. The results of this study showed that IL-4 had bifunctional effects on airway remodeling, one was the suppression of the proliferation of the ASM cells and the other was the promotion of VEGF release by the ASM cells, and amphiregulin can promote human ASM cell proliferation.
Shim
Jung Yeon
JY
Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. jy7.shim@samsung.com
Park
Sang Wook
SW
Kim
Deok Soo
DS
Shim
Jae Won
JW
Jung
Hye Lim
HL
Park
Moon Soo
MS
D066258:Amphiregulin; D001980:Bronchi / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D066255:EGF Family of Proteins; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D015847:Interleukin-4 / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C587848:AREG protein, human; D066258:Amphiregulin; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D016207:Cytokines; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4